9UU7

The crystal structure of human DEAD-box RNA helicase DDX28 RecA1 domain in complex with ADP

Summary for 9UU7

• Entry DOI: 10.2210/pdb9uu7/pdb
• Descriptor: Probable ATP-dependent RNA helicase DDX28, PHOSPHATE ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: dead-box rna helicase, mitoribosome assembly, ribosomal protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 50183.37

Authors

Lv, M.Q.,Cui, J. (deposition date: 2025-05-06, release date: 2026-03-04, Last modification date: 2026-05-27)

Primary citation

Cui, J.,Li, M.,Wang, L.,Li, F.,Ruan, K.,Lv, M.,Shi, Y.
Molecular mechanism underlying the specific RNA recognition of mitochondrial helicase DDX28 and its critical role in mitoribosomal biogenesis.
Structure, 34:853-, 2026

PubMed Abstract: Mitochondrial ribosome biogenesis depends on RNA helicases such as DDX28, a DEAD-box helicase that plays an essential role during early mitoribosome large-subunit assembly by interacting with 16S rRNA. Here, we demonstrate that the helicase core domain of DDX28 binds sequence and structure specifically to the H88_L stem-loop in 16S rRNA, with the RecA2 domain residue M431 as a key determinant for substrate selectivity. The N-terminal disordered region of DDX28 enhances nonspecific RNA binding but does not contribute to enzymatic activity. Furthermore, DDX28 deficiency disrupts mitochondrial translation, impairs OXPHOS complex assembly, and leads to metabolic dysfunction, including reduced membrane potential, elevated ROS, and suppressed glycolysis. Transcriptomic and metabolomic analyses reveal a compensatory upregulation of ribosome biogenesis genes alongside a dysregulation of the TCA cycle, oxidative phosphorylation, and lipid metabolism. Our integrated structural and functional study establishes DDX28 as an essential factor for mitoribosome assembly with potential links to mitochondrial disorders.

PubMed: 41819091
DOI: 10.1016/j.str.2026.02.009

Experimental method

X-RAY DIFFRACTION (2.6 Å)